A method has been developed for inserting one DNA molecule covalently into another and has been used to insert the galactose operon of E. coli into the DNA of the oncogenic virus SV40. This method and a related one will be used to approach the following objectives: (1) Transfer specific genes from prokaryotic cells to mammaliam cells in culture and establish the prokaryotic genes stably and heritably in the mammalian cells. (2) Determine whether prokaryotic gene expression occurs in eukaryotic cells to give functional proteins. If prokaryotic gene expression occurs, then: (3) Select mutations in the genes of SV40 controlling oncogenic transformation. (4) Select chain termination codon suppressor mutants in mammalian cells. (5) Develop a model system for isolating specific genes from E. coli by inserting them into a plasmid DNA molecule which can be reintroduced into E. coli. (6) Use this model system to isolate and amplify human ribosomal RNA genes and attempt to select, isolate, and amplify other specific mammalian cell genes.